title: Inhibition of anthrax lethal factor by curcumin and chemically modified curcumin derivatives.
abstract: Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric (Curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. We have investigated the inhibitory activities of curcumin and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the proteolytic component of anthrax toxin produced by the bacterium Bacillus anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF through a mixture of inhibitory mechanisms, without significant compromise to the binding of oligopeptide substrates, and one CMC derivative in particular, Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting LF with potency comparable with the parent compound, while also showing improved solubility and stability. The quantitative reduction in catalytic activity achieved by the different CMC derivatives appears to be a function of the proportion of the multiple mechanisms through which they inhibit the enzyme.
authors.affiliation: Department of Pathology .
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Antonelli
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lorne M
authors.initials: LM
authors.lastname: Golub
authors.forename: Francis
authors.initials: F
authors.lastname: Johnson
authors.forename: Sanford R
authors.initials: SR
authors.lastname: Simon
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001408:Bacillus anthracis / Q000737:chemistry / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055162:Biocatalysis; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; C030325:anthrax toxin; D003474:Curcumin
keywords: Anthrax; chemically modified curcumin; curcumin; lethal factor; metalloproteinase